We propose to investigate the carcinogenic effects of asbestos, chrysotile and crocidolite, following long-term oral administration to mice and rats, in relation to the etiology of gastro-intestinal tract cancer and cancers at other sites. We also propose to investigate the possible role of multiple factors in gastro-intestinal tract carcinogenesis, with particular reference to possible synergistic or other in vivo interactions between asbestos and known gastro-intestinal tract carcinogens. Chrysotile and crocidolite will be administered bi-weekly by gavage to group of 50 male and female mice and rats, commencing at weaning, at doses of 25 and 100 mg/kg for 24 months. The possible role of multiple factor interactions will be investigated by combined administration of chrysotile, and NMUT, a "direct-acting" nitrosamide carcinogen, or DMH, an "indirect-acting" hydrazine carcinogen; control groups will receive NMUT or DMH alone, administered weekly for 6 months by gavage at 1.25 mg/kg or by subcutaneous injection at 20 mg/kg, respectively, or chrysotile alone by b-weekly gavage at 25 mg/kg for 24 months. In both the asbestos carcinogenicity and the interaction studies, moribund animals and those surviving to 30 months will be sacrificed for histopathological examination.